The overall objective and long-term goal of the proposed research is to continue detailed studies of the structure of proteins involved in the blood coagulation process, and particularly those involved in the activation of prothrombin. These studies include assessment of the primary structure of these proteins, and the specific relationships between the primary structure and the function of these proteins. Studies of congenitally abnormal prothrombins and the prothrombins which are abnormal by virtue by vitamin-K antagonist therapy will assess the contributions of different elements of structure to prothrombin and thrombin function. Four project areas are envisioned at the present time. 1) The elucidation of the structural defects in prothrombin "Quick", prothrombin "Cardeza, and prothrombin "San Juan"; 2) initiation of primary structural studies on the bovine factor V molecule; 3) elucidation of the structural effects of long-term coumadin therapy on the carboxylation of specific residues in the prothrombin molecule; 4) chemical modification studies aimed at interpreting structure-function relationships in the prothrombin molecule.